Microbubble-mediated ultrasound therapy: a review of its potential in cancer treatment.
Microbubble-mediated ultrasound therapy: a review of its potential in cancer treatment.
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DOI：
10.2147/dddt.s31564
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Esener S
中科院分区：
文献类型：
--
作者：
Ibsen S;Schutt CE;Esener S
化疗药物的固有毒性是它们杀死癌细胞的必要条件，但也是患者所经历的有害副作用的来源。减少这些副作用的一种策略是通过将药物包封在载体中来限制健康组织暴露，所述载体在循环中表现出非常低的泄漏率，同时一旦进入肿瘤内就具有快速释放的潜力。设计具有这两种相反性质的载体是药物递送领域的主要挑战。需要触发事件来将车辆从其稳定的循环状态改变到其不稳定的释放状态。通过利用微泡与超声相互作用时发生的尺寸变化，可以实现独特的机械致动型触发器。这些机械驱动可以使脂质体和细胞膜破裂，从而允许快速药物释放并促进递送到附近的细胞中。超声波的紧密聚焦能力仅为几立方毫米，可以精确控制微泡使载体不稳定的组织位置。这使得超声波能够突出肿瘤组织，并导致药物从任何载体中快速释放。已经证明了不同的载体设计，从仅在微泡本身的表面上携带药物到将微泡沿着药物一起封装在脂质体内。在未来，纳米粒子可能会延长这些超声可降解药物输送车辆的循环半衰期作为超声诱导的机械驱动的成核位点。除了药物递送能力之外，微泡尺寸的变化还可以用于创建成像造影剂，其可以允许研究肿瘤的内部化学环境，以帮助改善癌症的诊断和检测。从循环药物递送载体获得真正肿瘤特异性释放的能力是减少化疗副作用同时增加药物有效性的令人兴奋的未来前景。
The inherently toxic nature of chemotherapy drugs is essential for them to kill cancer cells but is also the source of the detrimental side effects experienced by patients. One strategy to reduce these side effects is to limit the healthy tissue exposure by encapsulating the drugs in a vehicle that demonstrates a very low leak rate in circulation while simultaneously having the potential for rapid release once inside the tumor. Designing a vehicle with these two opposing properties is the major challenge in the field of drug delivery. A triggering event is required to change the vehicle from its stable circulating state to its unstable release state. A unique mechanical actuation type trigger is possible by harnessing the size changes that occur when microbubbles interact with ultrasound. These mechanical actuations can burst liposomes and cell membranes alike allowing for rapid drug release and facilitating delivery into nearby cells. The tight focusing ability of the ultrasound to just a few cubic millimeters allows for precise control over the tissue location where the microbubbles destabilize the vehicles. This allows the ultrasound to highlight the tumor tissue and cause rapid drug release from any carrier present. Different vehicle designs have been demonstrated from carrying drug on just the surface of the microbubble itself to encapsulating the microbubble along with the drug within a liposome. In the future, nanoparticles may extend the circulation half-life of these ultrasound triggerable drug-delivery vehicles by acting as nucleation sites of ultrasound-induced mechanical actuation. In addition to the drug delivery capability, the microbubble size changes can also be used to create imaging contrast agents that could allow the internal chemical environment of a tumor to be studied to help improve the diagnosis and detection of cancer. The ability to attain truly tumor-specific release from circulating drug-delivery vehicles is an exciting future prospect to reduce chemotherapy side effects while increasing drug effectiveness.